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Canine Genome decoded

Over time blocks of chromosomes travelling together have been broken down into short blocks with different flavors in the whole dog population (top panel). As dog breeds were created, a few chromosomes were selected for each breed. The blocks have not had a chance to break apart and are still long within breeds. This means that it is 50-times easier to find disease genes in dog breeds than in humans.

BOSTON — The genetic makeup of cancer is the next target for researchers at the Broad Institute after the successful mapping of the canine genome.

Scientists at The Broad Institute at MIT and Harvard decoded 99 percent of the canine genome by mapping a purebred female Boxer and sampling the genomes of 10 other dog breeds, coyotes and wolves to unveil 2.5 million individual genetic differences.

The finding is expected to help pinpoint diseased genes in dogs, taking veterinary medicine to another level, says Eric Lander, senior author of the paper, director of the Broad Institute, professor of biology at MIT and systems biology at Harvard Medical School.

"A natural progression of finding diseased genes is the development of a genetic test, furthering veterinarians' ability to predict a defect in a bloodline or caution owners a specific disease might be present in their pet," says Dr. Kerstin Lindblad-Toh, first author of the paper and co-director of the genome sequencing and analysis program at Broad. "I think this discovery will affect veterinarians a lot, especially in the next couple of years as diseased genes are found and genetic tests become available. Veterinarians will be able to give owners advice on what to feed and care for specific pets in effort to deter disease development or progression."

By comparing single nucleotide polymorphisms (SNP's), which serve as markers to locate genetic factors to physical, behavioral and medical traits, scientists can pinpoint the genes responsible for certain diseases.

"Our biggest breakthrough was discovering that very large chunks of genes travel together in dogs," Lindblad-Toh says. "This means it should be relatively easy to find the diseased genes in dogs. Also, the clustering of regulatory sequences is interesting because it means a subset of crucial human genes are under more elaborate control than what was previously thought."

Sequence method

The Whole Genome Shotgun (WGS) method was used to sequence the canine genome. With a total of 31.5 million sequence reads, about 7.5-fold sequence redundancies were assembled using the ARACHNE program with an initial assembly on the structure.

"Hardly any of the functional elements conserved between human and dog have been deleted in the mouse lineage, suggesting there is a common set of functional elements across all three mammalian species, corresponding to 5 percent of the human genome," Lindblad-Toh says.

Breeds

Selective breeding, carrying large genomic regions of several million bases of DNA into breeds, creating haplotype blocks, has reshaped the dog genome. The genomic regions are predicted to find genes responsible for disease, body size and behavior, Lander says.

"Since breeding tends to predispose many dog breeds to genetic diseases, the dog genome and SNP map, veterinarians will have the tools to identify the diseased genes," Lander adds.

Another finding with the research is that the dog, human and mouse share 5 percent of the same genome.

"Some pieces of the genome must stay the same throughout evolution to maintain functions and keep humans-human and dogs-dogs, instead of turning into a completely different animal," Lindblad-Toh says.